Increased microglial activation in patients with Parkinson disease using [$^{18}$F]-DPA714 TSPO PET imaging

Sonia Lavisse (1, 2) , Sébastien Goutal (1, 2) , Catriona Wimberley (3) , Mattéo Tonietto (3) , Michel Bottlaender (3, 4) , Philippe Gervais (3) , Bertrand Kuhnast (3) , Marie-Anne Peyronneau (3) , Olivier Barret (1, 2) , Julien Lagarde (5, 3, 6, 7) , Marie Sarazin (5, 3, 6, 7) , Philippe Hantraye (1, 2) , Claire Thiriez (8, 9) , Philippe Remy (1, 8, 9, 2)

1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
2 MIRCEN - Molecular Imaging Research Center [Fontenay-aux-Roses]
3 BIOMAPS - LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay
4 UNIACT - Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle
5 UPCité - Université Paris Cité
6 GHU Paris Psychiatrie et Neurosciences
7 Centre Hospitalier Sainte Anne [Paris]
8 IMRB - Institut Mondor de Recherche Biomédicale
9 CHU Henri Mondor [Créteil]

Introduction: Increasing evidence suggests that neuroinflammation is active in Parkinson disease (PD) and contributes to neurodegeneration. This process can be studied in vivo with PET and radioligands targeting TSPO, upregulated in activated microglia. Initial PET studies investigating microglial activation in PD with the [$^{11}$C]-PK11195 have provided inconclusive results. Here we assess the presence and distribution of neuroinflammatory response in PD patients using [$^{18}$F]-DPA714 and to correlate imaging biomarkers to dopamine transporter imaging and clinical status.Methods: PD patients (n = 24, Hoehn and Yahr I-III) and 28 healthy controls were scanned with [$^{18}$F]-DPA714 and [$^{11}$C]-PE2I and analyzed. They were all genotyped for TSPO polymorphism. Regional binding parameters were estimated (reference Logan graphical approach with supervised cluster analysis). Impact of TSPO genotype was analyzed using Wilcoxon signed-rank test. Differences between groups were investigated using a two-way ANOVA and Tukey post hoc tests.Results: PD patients showed significantly higher [$^{18}$F]-DPA714 binding compared to healthy controls bilaterally in the midbrain (p < 0.001), the frontal cortex (p = 0.001), and the putamen contralateral to the more clinically affected hemibody (p = 0.038). Microglial activation in these regions did not correlate with the severity of motor symptoms, disease duration nor putaminal [$^{11}$C]-PE2I uptake. However, there was a trend toward a correlation between cortical TSPO binding and disease duration (p = 0.015 uncorrected, p = 0.07 after Bonferroni correction).Conclusion: [$^{18}$F]-DPA714 binding confirmed that there is a specific topographic pattern of microglial activation in the nigro-striatal pathway and the frontal cortex of PD patients.

Mots clés: PET; Parkinson disease; TSPO[$^{18}$F]-DPA714; Microglia; Neuroinflammation

Domaines: Sciences du Vivant [q-bio]

Sonia Lavisse, Sébastien Goutal, Catriona Wimberley, Mattéo Tonietto, Michel Bottlaender, et al.. Increased microglial activation in patients with Parkinson disease using [$^{18}$F]-DPA714 TSPO PET imaging. Parkinsonism & Related Disorders, 2021, 82, pp.29 - 36. ⟨10.1016/j.parkreldis.2020.11.011⟩. ⟨hal-03493070⟩